1. Field of the Invention
The current invention relates to the field of non-invasive blood analyte measurement. More particularly, the current invention relates to a compact instrument for non-invasive blood analyte determination that employs light emitting diodes (LED""s) supported on a thermally stable substrate as a source of light energy.
2. Description of Related Art
Conventional methods of clinical testing have required the use of invasive procedures, such as biopsy and phlebotomy, to sample blood and tissue. Subsequently, the samples were transported to a central location, such as a laboratory, for examination and analysis. There is an increasing trend, however, toward point-of care testing, and even in-home testing. A benefit of this trend is to minimize the turnaround time from when a sample is taken to being able to take action based on test results. At the same time, sampling procedures are becoming less and less invasive. Since they minimize or eliminate the need to handle blood and tissue specimens, minimally invasive and non-invasive procedures drastically reduce biohazard risk, both to the subject and to the practitioner.
The goal of non-invasive blood analyte measurement is to determine the concentration of targeted blood analytes without penetrating the skin. Near infrared (NIR) diffuse reflectance spectroscopy is a promising technology for noninvasive blood analyte measurement and involves the illumination of a spot on the body with low energy near-infrared light (750-2500 nm). The light is partially absorbed and scattered, according to its interaction with chemical components within the tissue, prior to being reflected back to a detector. The detected light is used to create a graph of xe2x88x92log R/Rs, where R is the reflectance spectrum of the skin and Rs is the reflectance of an instrument standard. In infrared spectroscopy, this graph is analogous to an absorbance spectrum containing quantitative information that is based on the known interaction of the incident light with components of the body.
Portable and handheld noninvasive blood glucose analyzers are being developed for point of care and in home use. The development of such devices has been hindered, in part, by the type of light source commonly used in spectrometer instruments. The conventional halogen tungsten lamp found in most spectrometer instruments is large and energy inefficient. It has a high power requirement, thus shortening battery life, generates excessive amounts of heat, requires a long time to stabilize and has a short life expectancy.
Furthermore, conventionally, light emitted from a light source is coupled into an optical probe, or otherwise directed toward a measurement site using space optics consisting of sets of mirrors and lenses. Such arrangements have high space requirements and they are highly vulnerable to mechanical shock.
The prior art provides a few examples of light source assemblies for non-invasive optical sampling. For example, F. Levinson, Light mixing device with fiber optic output, U.S. Pat. No. 5,271,279 (Dec. 14, 1993) describes a light-mixing device for a spectroscopic instrument in which a mixing rod couples light from a light source composed of LED""s, die bonded into an electric header, with a plurality of optical fibers. The LED""s have differing central wavelengths of emitted light and the mixing rod efficiently mixes the output of the several LED""s into a single beam of light and then splits the beam in uniform fashion across the several optical fibers. The described device does not provide any means of collecting light energy emitted from a sample. It also doesn""t provide any means of shaping light as it is emitted from the individual LED""s. While the header of the LED assembly acts as a conduit for excess thermal energy produced by the LED""s, it would be desirable to provide an active cooling element to provide an environment that maximizes energy efficiency of the LED""s.
R. Rosenthal, Light probe for a near infrared body chemistry measurement instrument, U.S. Pat. No. 6,134,458 (Dec. 31, 1991) describes a light probe for a spectroscopic instrument that includes an illumination ring having external facets. LED""s positioned about the facets emit light into the illumination ring; light is coupled to the measurement site by bringing the body part bearing the site into contact with the illumination ring. An optical detector is located coaxially with the illumination ring. While the Rosenthal device does provide a means of collecting light energy emitted from the site, it doesn""t provide any means of mixing the light energy emitted from the several LED""s. The light from the LED""s is coupled directly with the probe, without the interposition of a mixer to thoroughly blend the wavelength content of the light. The Rosenthal device also does not provide any means of shaping the light beams emitted from the LED""s, nor does it provide a thermally stable substrate for the LED""s. Furthermore, no active cooling system is provided to optimize operating temperature of the LED""s.
Spectrometer instruments for measuring concentration of blood analystes such as glucose are known. Typically, such devices are not intended to be portable. For example, K. Kaffka, L. Gyarmati, I. Vxc3xa1lyi-Nagy, I. Gxc3x6dxc3x6lle, G. Domjxc3xa1n, J. Jxc3xa1ko, Method and apparatus for rapid non-invasive determination of blood composition parameters, U.S. Pat. No. 5,947,337 (Oct. 26, 1999) describe an instrument for non-invasive glucose measurement. The described instrument irradiates the distal phalanx of a subject""s finger with light in the near IR. The transmitted or reflected radiation is detected and analyzed and an estimate of blood glucose level made. There is no indication that the device described by Kaffka, et aL is portable or handheld. The signal is coupled with a fiber optic probe by means of a conventional arrangement of lenses and mirrors. The space requirements of such an arrangement are unsuited to a handheld device. Illumination fibers and collection fibers are provided in separate structures, also requiring excessive amounts of space.
M. Block, L. Sodickson, Non-invasive, non-spectrophotometric infrared measurement of blood analyte concentrations, U.S. Pat. No. 5,424,545 (Jun. 13, 1995) describe an instrument for noninvasive blood analyte determination that relies on calorimetric analysis to arrive at a blood analyte determination. The described device is not handheld or portable. As with the previous reference, a light beam is coupled with an illumination fiber by means of lenses and mirrors, with similar disadvantages.
T. Aldrich, Non-invasive blood component analyzer, U.S. Pat. No. 6,064,898 (May 16, 2000) describe a non-invasive blood component analyzer that also provides built-in path length monitoring to allow use in subjects of varying finger size. The Aldrich device is not a handheld or otherwise portable device. It provides a light source either from LED""s or from a lamp. No structure is provided for coupling the light beam from the light source; the light is simply emitted in the vicinity of the sampling site and coupled through the atmosphere. The current device, plus all of the previously described devices for blood analyte determination, while they often employ several LED""s as a light source, do not provide the LED""s in structured arrays; and they do not provide substrates to lend the LED""s mechanical support, thermal stability and electrical connectivity.
Handheld spectrometers are known in the prior art. K. Levin, S. Kerem, V. Madorsky, Handheld infrared spectrometer, U.S. Pat. No. 6,031,233 (Feb. 29, 2000) describe a handheld infrared spectrometer. Space is conserved by aligning the optics and eliminating fibers. Light is emitted from a conventional lamp and passed through an acousto-optical tuning filter (AOTF) for wavelength selection. The filtered light is focused through one or more lenses and directed toward the measurement site through a window. While the design is highly spaceefficient, allowing for a truly handheld spectrometer, the use of an AOTF for wavelength selection requires a wavelength synthesizer and an RF amplifier. Furthermore, a conventional lamp for a light source is energy inefficient, shortening battery life and generating excessive amounts of thermal energy.
H. Van Aken, A. Kravetz, K. Garde, W. Weber, J. Corrado, Handheld portable spectrometer, U.S. Pat. No. 5,319,437 (Jun. 7, 1994) describe a handheld spectrometer. The Van Aken device employs a conventional lamp, with all of its attendant disadvantages.
An example of a portable noninvasive blood glucose analyzer is provided by R. Rosenthal, Instrument for non-invasive measurement of blood glucose, U.S. Pat. No. 5,077,476 (Oct. 17, 2000). Rosenthal describes a hand-held instrument for non-invasive measurement of glucose. One or more LED""s are used to provide a point source of near IR energy of a predetermined bandwidth. The emitted energy is coupled with the sampling site by means of a focusing lens. The Rosenthal instrument does not provide a wide band signal from an array of LED""s emitting in overlapping wavelength regions. The space requirements for the mirror arrangement and the detector arrangement are such that the overall size of the instrument would be unwieldy for a handheld device. The Rosenthal device does not provide a spectrum analyzer or a linear detector array.
There exists, therefore, a need in the art for a long-lived, space efficient, energyefficient light source assembly for non-invasive optical sampling. It would be desirable to provide a light source assembly that employs light-emitting diodes (LED""s) as a light source. Furthermore, it would be desirable to combine the LED""s into a compact sub-assembly by attaching LED""s to a substrate that provided electrical connections, and mechanical and thermal stability. It would be a great advantage to provide a simple space-efficient means of coupling light from the light source with an optical probe that is resistant to mechanical shock and perturbation, while mixing wavelengths thoroughly and normalizing light intensity. It would be a further advantage to provide a means of optimizing the operating temperature to maximize LED efficiency. It would be a significant technological advance to incorporate such a light source assembly into a lightweight, compact instrument for non-invasive blood analyte determination.
In a first embodiment, the invention provides a LED-based light source assembly for non-invasive optical sampling. A wide band signal is achieved by combining LED""s, singly or in groups, that emit in overlapping wavelength bands. LED""s are combined into a LED/substrate sub-assembly, in which LED""s, attached to reflectors mounted in a thermally stable substrate, are electrically connected by means of bonding wires. A LED light source assembly includes the LED/substrate sub-assembly; a mixer, consisting of a large diameter fiber optic having a hollow center to couple the signal to a probe; a collection fiber, threaded through the hollow center, for collecting light emitted from the sample under test; a printed circuit board, in which the LED/substrate sub-assembly is seated, and having electrical contacts for connecting the LED""s to an LED driver; and a cooling system for stabilizing the substrate temperature.
In a second embodiment, the invention provides a compact, lightweight instrument for non-invasive blood analyte determination that incorporates the light source assembly provided by the first embodiment. The instrument includes the LED-based light source assembly; an optical module that includes a miniature spectrum analyzer having a grating to focus and disperse the light received from the collection fiber and a linear detector array for receiving the dispersed spectrum; an LED driver; a digital electronics module for processing the spectrum and estimating concentration of a target analyte; and a display, for outputting the target analyte concentration.
The high conversion efficiency of the light source results in extremely low power dissipation and virtually no heat generation, making incorporation of the light source and the spectrometer into a single unit practicable. High-speed pulsing of the signal allows application of high-sensitivity, synchronous detection techniques. Speed and flexibility in sequencing LED""s allows simultaneous measurement and skin temperature control.